Patent GB-1104412-A (GB)
Title: Nitroimidazole derivatives
IPC: C07D233/95
Filed: 1965-03-01
Abstract: Novel compounds of general formula <FORM:1104412/C2/1> where Ar is an aromatic triyl radical; r1 is H, C1- 5 alkyl or -(CH2)nX where n is 2, 3 o 4, and X is halo, OH or C1- 5 alkoxy; r2 is H, NO2, halo, amino, carboxamido, sulphonamido or C1- 5 alkoxy; r3 is H, C1- 5 alkyl, carboxy, aryl, halo, hydroxy, amino, mono- or di-(C1- 5) -alkylamino, acylamino, haloalkyl, NO2, sulphonamido, mono- or di-(C1- 5 alkyl) sulphonamido, C1- 5 alkoxy, cyano, C1- 5 alkylthio, carboxamido, mono- or di-(C1- 5 alkyl) carboxamido, formyl, C2- 6 alkanoyl, acylamino-(C1- 5)-alkyl, mono- or di-(C1- 5 alkyl) -amino-(C1- 5)-alkyl, N1-morpholino-(C1- 5)-alkyl, N1-piperidino-(C1- 5) - alkyl, N1 - pyrrolidino - (C1- 5) - alkyl, hydroxy - (C1- 5) - alkyl, C1- 5 - alkoxyimino carbonyl, amidino, mono- or di-(C1- 5)-alkyl-amidino, carboxyhydrazido, (C1- 5 alkoxy)-carbonyl or (C1- 5 alkyl) sulphonyl; and one of r4 or r5 is nitro and the other H; are prepared by nitration of the compound where r4 and r5 are both H, optionally followed by introduction of r1 which may be then modified; and also optionally with simultaneous introduction of NO2 or Ar and/or modification of r2 and r3 substituents; and novel compounds of general formula <FORM:1104412/C2/2> where m is 1 or 2; Ar is aromatic triyl, R27 is H, NO2, halo, sulphonamido or carboxamido; R28 is H, carboxy, aryl, halo, OH, mono- or di-(C1- 5)-alkylamino, NO2, sulphonamido, mono- or di-(C1- 5 alkyl)-sulphonamido, cyano, carboxamido, mono- or di-(C1- 5 alkyl)-carboxamido, formyl, C2- 6 alkanoyl, C1- 5 alkyl, mono- or di-(C1- 5 alkyl) amino-(C1- 5)-alkyl, N1-morpholino-(C1- 5) - alkyl, N1 - piperidino - (C1- 5) - alkyl, N1 - pyrrolidino - (1- 5) - alkyl, hydroxy - (C1- 5)-alkyl or C1- 5 alkylsulphonyl; and one of R4 or R5 is NO2 and the other H are prepared by cyclization of the corresponding 2-(haloalkylaryl) -4-nitroimidazole.  Intermediates of the first general formula above wherein r1 = r4 = r5 = H are prepared either by treating the corresponding substituted aromatic aldehyde with glyoxal and ammonium hydroxide or by cyclization of a substituted aromatic amidine of formula <FORM:1104412/C2/3> which itself is prepared by reaction of the ethoxy acetal of aminoacetaldehyde and a compound of formula <FORM:1104412/C2/4> Substituted - 2 (haloalkylaryl) - 4 - nitroimidazoles are prepared from an orthodicyano aromatic compound, e.g. 1,2-dicyanobenzene, which is treated with ethanol and HCl to give the o-cyanoaryl imidate, which is treated with aminoacetaldehyde acetal to give an o-cyanoaryl amidine, which is cyclized to the 2-(o-carboxyaryl) imidazole with acid and then nitrated to give the 2-(o-carboxyaryl)-4-nitroimidazole, which is reduced with diborane to the 2 - (21 - hydroxymethylaryl) - 4 - nitroimidazole, then halogenated optionally, followed by chain extension via the cyanomethyl, carboxymethyl and hydroxyethyl route to give the 2-haloethyl compound.  3,4-Dichlorobenzonitrile is prepared by dehydration of the amide.  p-Cyanobenzamide is prepared from the p-cyanobenzoic acid.  Pharmaceutical compositions in conventional forms for oral, topical or vaginal administration and finding use as parasiticides, e.g. antiprotozoals, comprise an above novel compound and a carrier or excipient including food.